Unless otherwise indicated herein, the materials described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.
Proteomics seeks to understand how proteins function in their native environment with the overall intention of gaining an understanding of their biological function. One aspect of proteomics deals with the quantitative study of protein expression, which can help identify the main proteins found in a particular sample. Another aspect of proteomics deals with the qualitative and/or quantitative study of protein expression between samples that differ by certain variables, which can help identify proteins that are differentially expressed in related samples, e.g. when comparing the protein composition and abundance in pathologically altered cells contrasted with normal, healthy cells.
A challenge to the analysis of proteins from these biological samples is the complexity of the samples, which often consist of numerous proteins in varying abundances. Measuring the abundance of the various proteins in biological samples is currently a challenging, labor intensive task. High-throughput technologies have been developed for such measurements, the most commonly applied technology being mass spectrometry (MS)-based techniques such as tandem-MS technologies. However, the total throughput of these types of measurements is limited by the mass spectrometer, which is an inherently serial device.
Nucleic acid macromolecules (e.g. DNA or RNA) known as aptamers have been utilized to detect the presence of particular proteins. In these techniques, an aptamer designed to bind tightly to a specific molecular target, such as a protein, is mixed with the sample. Standard techniques are then utilized to detect the aptamer, which indicates the presence of the target protein in the sample. For example, Shuber (U.S. Pat. No. 8,852,893) describes methods of using an aptamer to detect a particular protein in a sample. Methods have also been developed for using aptamers to quantify the amount of particular proteins in a sample. For example, Gold et al. describe an aptamer-based method capable of simultaneously measuring hundreds proteins from a small sample volume (Gold L, Ayers D, Bertino J, et al. Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery. Gelain F, ed. PLoS ONE. 2010; 5(12):e15004. doi:10.1371/journal.pone.0015004).
A common feature of these aptamer techniques is that each aptamer has been designed to bind to one particular target protein. A number of such aptamers are combined to create an aptamer library capable of detecting and/or quantifying a number of proteins. Using such techniques, a library on the order of tens of thousands of aptamers would be needed to achieve complete coverage of an entire proteome of a human cell.